Dental caries, or tooth decay, results from the erosion of mineral in the enamel and underlying dentin layers of the tooth by the lactic acid secreted by a discrete class of streptococcal bacteria. These cariogenic bacteria, collectively called “mutans streptococci” have been genetically classified into at least four distinct species: Streptococcus mutans, S. rattus, S. cricetus, and S. sobrinus. Of these, S. mutans, and, to a lesser extent, S. sobrinus, are common human pathogens. The biology and cariogenic potential of these organisms has been reviewed by A. L. Coykendall and K. B. Gustafson, Taxonomy of Streptococcus mutans, in Molecular Microbiology and Immunobiology of Streptococcus mutans. (S. Hamada et al. eds., 1986), Elsevier Science Publishers B. V.; Loesche et al., Microbiol. Rev. 50(4):353–80 (1986); and Hamada and Slade, Microbiol. Rev. 44(2):331–84 (1980) (incorporated herein by reference).
In the initial stage of infection, mutans streptococci attach to the dental pellicle, or outer covering of the tooth, through bacterial adhesion proteins (e.g., AgI/II protein) specific for pellicular carbohydrates. At this stage, the bacteria present merely a potential threat to dental integrity and are easily removed. However, once this toehold is established, vast numbers of bacteria may accumulate on the tooth surface as dental plaque.
Dental plaque is primarily comprised of bacteria bound together with high molecular weight carbohydrate polymers. These branched, α-1,3 and α-1,6-linked glucose polymers (glucans) are synthesized from sucrose by a family of extracellular glucosyltransferases or GTFs, constitutively secreted by the cariogenic mutans streptococci. The various GTFs each produce a different form of glucan, broadly classified as either water soluble (WSG) or water insoluble (WIG). Together, these glucans form the basic scaffolding for the aggregation of mutans—and other oral streptococci—through interaction with the catalytic GTFs and nonpolymerizing glucan-binding proteins (GBPs).
The resulting accretion of bacteria and extracellular polysaccharides (plaque) concentrates lactic acid secretions on the tooth surface, shielding the acid from the buffering and dispersing effects of saliva. Chronic lactic acid exposure dissolves the hydroxyapatite of the dentin enamel, allowing bacterial access to the underlying dentin, and ultimately, to the soft, highly sensitive pulp.
Because mutans streptococci require a hard surface for attachment and plaque formation, these bacteria do not thrive in the predentate mouth. Rather, the neonatal oral cavity contains other maternally-derived bacterial flora, primarily the non-cariogenic Streptococcus salivarius and Streptococcus mitis, which colonize soft epithelial surfaces. Interestingly, the eruption of primary teeth does not result in the immediate colonization of cariogenic streptococci. Rather, and for reasons that are not entirely understood, newly erupted dental surfaces do not usually support the attachment of mutans, but are often colonized by noncariogenic S. sanguis. Subsequently, however, oral colonization with mutans streptococci occurs between about eighteen and thirty-six months of age. Although this “window of infectivity” between tooth eruption and mutans colonization remains a poorly understood phenomena, it nevertheless provides a potential opportunity to block mutans invasion before it starts.
Like most infections, mutans streptococcal infections elicit antibody responses in the host, and mounting evidence suggests that a healthy immune system is critical to oral health. Indeed, a low incidence of dental caries has been correlated with high levels of IgG antibodies to mutans surface proteins. Although IgG is usually not considered a secreted protein, antibodies of this isotype may access mutans streptococci at the gumline, through the gingival crevice. Moreover, anti-mutans IgA antibodies, secreted directly into the salivary milieu, appear to block bacterial attachment and plaque formation.
Mutans streptococcal infection is arguably the most common bacterial disease in humans. Moreover, the tooth decay generated by these bacteria represent the principal cause of tooth loss among adults below the age of forty. A properly directed vaccine could reduce the incidence of caries in infected adults. In addition, because children are immunocompetent by this age (Smith and Taubman, Crit. Rev. Oral Biol. Med. 4(3/4):335–41 (1993)), early vaccination could even prevent mutans colonization entirely, potentially resulting in a caries-free mouth.
Thus, the possibility of controlling this caries by active immunization is currently under intensive investigation. The various strategies for creating a prophylactic caries vaccine are reviewed in Immunologic Aspects of Dental Caries: Selection of Immunogens for a Caries Vaccine and Cross Reactivity of Antisera to Oral Microorganisms with Mammalian Tissues (W. Bowen, R. Genco & T. O'Brien eds. 1976) Information Retrieval Inc.; and D. J. Smith and M. A. Taubman, Vaccines Against Dental Caries Infection in New Generation Vaccines (M. M. Levine, G. C. Woodrow, J. B. Kaper, & G. S. Cobon eds., 2d ed. 1997), Marcel Dekker, Inc., (each of which are incorporated herein by reference). These attempts range from oral ingestion of highly cariogenic strains of whole, killed S. mutans bacteria (Michalek et al., Science 192:1238–40 (1996)), to parenteral vaccines using peptides from critical regions of GTF or AgI/II proteins. None of these vaccines has, by themselves, proved to be a panacea against cariogenic infection.
Thus, there remains a need in the art for a safe and efficacious vaccine against mutans streptococci.